Correlation between copy number variation genes (focal events) and molecular subtypes
Cholangiocarcinoma (Primary solid tumor)
28 January 2016 | analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C13B5ZHN
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between copy number variation genes (focal events) and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C13B5ZHN
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and molecular subtypes.

Summary

Testing the association between copy number variation 20 focal events and 10 molecular subtypes across 36 patients, 18 significant findings detected with P value < 0.05 and Q value < 0.25.

- amp_11q13.3 cnv correlated to 'RPPA_CHIERARCHICAL'.

- del_1p36.21 cnv correlated to 'CN_CNMF', 'METHLYATION_CNMF', 'MRNASEQ_CNMF', and 'MRNASEQ_CHIERARCHICAL'.

- del_3p13 cnv correlated to 'CN_CNMF'.

- del_6q13 cnv correlated to 'CN_CNMF'.

- del_9q21.11 cnv correlated to 'RPPA_CHIERARCHICAL'.

- del_12q24.13 cnv correlated to 'CN_CNMF'.

- del_13q21.32 cnv correlated to 'CN_CNMF'.

- del_14q22.1 cnv correlated to 'RPPA_CHIERARCHICAL'.

- del_14q32.11 cnv correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.

- del_14q32.13 cnv correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.

- del_14q32.33 cnv correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.

- del_16q23.1 cnv correlated to 'MIRSEQ_CHIERARCHICAL'.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between significant copy number variation of 20 focal events and 10 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 18 significant findings detected.

|  | Clinical Features | CN CNMF | METHLYATION CNMF | RPPA CNMF | RPPA CHIERARCHICAL | MRNASEQ CNMF | MRNASEQ CHIERARCHICAL | MIRSEQ CNMF | MIRSEQ CHIERARCHICAL | MIRSEQ MATURE CNMF | MIRSEQ MATURE CHIERARCHICAL
| nCNV (%) | nWild-Type | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test
del 1p36 21 | 30 (83%) | 6 | 0.0168 (0.213) | 0.00218 (0.0872) | 0.106 (0.583) | 0.291 (0.719) | 0.00018 (0.0167) | 0.00883 (0.206) | 0.55 (0.797) | 0.128 (0.596) | 0.473 (0.763) | 0.255 (0.699)
del 14q32 11 | 20 (56%) | 16 | 0.00034 (0.017) | 0.00943 (0.206) | 0.267 (0.699) | 0.472 (0.763) | 0.0407 (0.37) | 0.0576 (0.421) | 0.908 (0.977) | 0.755 (0.916) | 0.355 (0.728) | 0.532 (0.777)
del 14q32 13 | 20 (56%) | 16 | 0.00025 (0.0167) | 0.0103 (0.206) | 0.265 (0.699) | 0.471 (0.763) | 0.0405 (0.37) | 0.0575 (0.421) | 0.908 (0.977) | 0.755 (0.916) | 0.356 (0.728) | 0.531 (0.777)
del 14q32 33 | 20 (56%) | 16 | 0.00021 (0.0167) | 0.0102 (0.206) | 0.267 (0.699) | 0.473 (0.763) | 0.0395 (0.37) | 0.0572 (0.421) | 0.909 (0.977) | 0.756 (0.916) | 0.354 (0.728) | 0.532 (0.777)
amp 11q13 3 | 8 (22%) | 28 | 0.411 (0.744) | 0.609 (0.84) | 0.152 (0.646) | 0.019 (0.213) | 0.518 (0.777) | 0.0448 (0.389) | 0.388 (0.728) | 0.971 (1.00) | 0.246 (0.699) | 0.719 (0.913)
del 3p13 | 28 (78%) | 8 | 0.0163 (0.213) | 0.364 (0.728) | 0.621 (0.84) | 0.373 (0.728) | 0.38 (0.728) | 0.289 (0.719) | 0.812 (0.935) | 0.241 (0.699) | 0.563 (0.81) | 0.371 (0.728)
del 6q13 | 21 (58%) | 15 | 0.0147 (0.213) | 0.119 (0.583) | 0.454 (0.763) | 0.179 (0.646) | 0.157 (0.646) | 0.252 (0.699) | 0.878 (0.975) | 0.344 (0.728) | 0.961 (1.00) | 0.916 (0.977)
del 9q21 11 | 19 (53%) | 17 | 0.0293 (0.309) | 0.492 (0.768) | 0.256 (0.699) | 0.0115 (0.209) | 0.162 (0.646) | 0.187 (0.649) | 0.251 (0.699) | 0.43 (0.754) | 0.298 (0.72) | 0.347 (0.728)
del 12q24 13 | 8 (22%) | 28 | 0.0192 (0.213) | 0.782 (0.935) | 1 (1.00) | 1 (1.00) | 1 (1.00) | 0.615 (0.84) | 0.811 (0.935) | 0.669 (0.886) | 0.721 (0.913) | 0.812 (0.935)
del 13q21 32 | 16 (44%) | 20 | 0.0175 (0.213) | 0.918 (0.977) | 0.526 (0.777) | 0.478 (0.764) | 0.0979 (0.576) | 0.875 (0.975) | 0.588 (0.834) | 0.488 (0.768) | 0.882 (0.975) | 0.513 (0.777)
del 14q22 1 | 14 (39%) | 22 | 0.0869 (0.561) | 0.575 (0.821) | 0.25 (0.699) | 0.00744 (0.206) | 0.383 (0.728) | 0.12 (0.583) | 0.88 (0.975) | 0.973 (1.00) | 0.832 (0.951) | 0.38 (0.728)
del 16q23 1 | 7 (19%) | 29 | 0.181 (0.646) | 0.274 (0.699) | 0.39 (0.728) | 0.429 (0.754) | 0.19 (0.649) | 0.413 (0.744) | 0.595 (0.838) | 0.019 (0.213) | 0.619 (0.84) | 0.702 (0.906)
amp 1q22 | 24 (67%) | 12 | 0.321 (0.728) | 0.367 (0.728) | 0.703 (0.906) | 0.74 (0.916) | 0.0589 (0.421) | 0.355 (0.728) | 1 (1.00) | 0.403 (0.74) | 0.163 (0.646) | 0.392 (0.728)
amp 12q13 2 | 10 (28%) | 26 | 0.271 (0.699) | 0.897 (0.977) | 0.0638 (0.44) | 0.192 (0.649) | 0.742 (0.916) | 0.91 (0.977) | 0.426 (0.754) | 0.518 (0.777) | 0.948 (1.00) | 0.47 (0.763)
del 3p25 3 | 28 (78%) | 8 | 0.109 (0.583) | 0.609 (0.84) | 1 (1.00) | 0.388 (0.728) | 0.122 (0.583) | 0.0702 (0.468) | 0.503 (0.777) | 0.761 (0.916) | 0.721 (0.913) | 0.221 (0.699)
del 4q34 3 | 23 (64%) | 13 | 0.255 (0.699) | 0.467 (0.763) | 0.111 (0.583) | 0.168 (0.646) | 0.347 (0.728) | 0.332 (0.728) | 0.264 (0.699) | 0.486 (0.768) | 0.507 (0.777) | 0.168 (0.646)
del 5q13 3 | 8 (22%) | 28 | 0.242 (0.699) | 0.276 (0.699) | 0.393 (0.728) | 0.3 (0.72) | 0.0497 (0.415) | 0.159 (0.646) | 1 (1.00) | 0.669 (0.886) | 0.735 (0.916) | 0.879 (0.975)
del 9p21 3 | 23 (64%) | 13 | 0.254 (0.699) | 0.472 (0.763) | 0.809 (0.935) | 0.159 (0.646) | 0.364 (0.728) | 0.16 (0.646) | 0.108 (0.583) | 0.621 (0.84) | 0.813 (0.935) | 0.122 (0.583)
del 10q26 12 | 12 (33%) | 24 | 0.861 (0.975) | 0.175 (0.646) | 1 (1.00) | 0.808 (0.935) | 0.698 (0.906) | 0.684 (0.9) | 0.456 (0.763) | 0.215 (0.699) | 0.464 (0.763) | 0.309 (0.728)
del 11q25 | 13 (36%) | 23 | 0.096 (0.576) | 1 (1.00) | 0.302 (0.72) | 0.0913 (0.571) | 0.364 (0.728) | 0.638 (0.857) | 0.796 (0.935) | 0.217 (0.699) | 0.726 (0.913) | 0.172 (0.646)

'amp_11q13.3' versus 'RPPA_CHIERARCHICAL'

P value = 0.019 (Fisher's exact test), Q value = 0.21

Table S1. Gene #2: 'amp_11q13.3' versus Molecular Subtype #4: 'RPPA_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 6 | 7 | 8 | 9
AMP PEAK 2(11Q13.3) MUTATED | 2 | 0 | 4 | 0
AMP PEAK 2(11Q13.3) WILD-TYPE | 4 | 7 | 4 | 9

Figure S1. Get High-res Image Gene #2: 'amp_11q13.3' versus Molecular Subtype #4: 'RPPA_CHIERARCHICAL'

'del_1p36.21' versus 'CN_CNMF'

P value = 0.0168 (Fisher's exact test), Q value = 0.21

Table S2. Gene #4: 'del_1p36.21' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 1(1P36.21) MUTATED | 8 | 9 | 7 | 6
DEL PEAK 1(1P36.21) WILD-TYPE | 6 | 0 | 0 | 0

Figure S2. Get High-res Image Gene #4: 'del_1p36.21' versus Molecular Subtype #1: 'CN_CNMF'

'del_1p36.21' versus 'METHLYATION_CNMF'

P value = 0.00218 (Fisher's exact test), Q value = 0.087

Table S3. Gene #4: 'del_1p36.21' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 14 | 10 | 12
DEL PEAK 1(1P36.21) MUTATED | 8 | 10 | 12
DEL PEAK 1(1P36.21) WILD-TYPE | 6 | 0 | 0

Figure S3. Get High-res Image Gene #4: 'del_1p36.21' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_1p36.21' versus 'MRNASEQ_CNMF'

P value = 0.00018 (Fisher's exact test), Q value = 0.017

Table S4. Gene #4: 'del_1p36.21' versus Molecular Subtype #5: 'MRNASEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6
--- | --- | --- | --- | --- | --- | ---
ALL | 6 | 4 | 5 | 6 | 9 | 6
DEL PEAK 1(1P36.21) MUTATED | 1 | 4 | 4 | 6 | 9 | 6
DEL PEAK 1(1P36.21) WILD-TYPE | 5 | 0 | 1 | 0 | 0 | 0

Figure S4. Get High-res Image Gene #4: 'del_1p36.21' versus Molecular Subtype #5: 'MRNASEQ_CNMF'

'del_1p36.21' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.00883 (Fisher's exact test), Q value = 0.21

Table S5. Gene #4: 'del_1p36.21' versus Molecular Subtype #6: 'MRNASEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7
--- | --- | --- | --- | --- | --- | --- | ---
ALL | 4 | 5 | 5 | 9 | 6 | 5 | 2
DEL PEAK 1(1P36.21) MUTATED | 1 | 4 | 4 | 9 | 6 | 5 | 1
DEL PEAK 1(1P36.21) WILD-TYPE | 3 | 1 | 1 | 0 | 0 | 0 | 1

Figure S5. Get High-res Image Gene #4: 'del_1p36.21' versus Molecular Subtype #6: 'MRNASEQ_CHIERARCHICAL'

'del_3p13' versus 'CN_CNMF'

P value = 0.0163 (Fisher's exact test), Q value = 0.21

Table S6. Gene #6: 'del_3p13' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 3(3P13) MUTATED | 7 | 8 | 7 | 6
DEL PEAK 3(3P13) WILD-TYPE | 7 | 1 | 0 | 0

Figure S6. Get High-res Image Gene #6: 'del_3p13' versus Molecular Subtype #1: 'CN_CNMF'

'del_6q13' versus 'CN_CNMF'

P value = 0.0147 (Fisher's exact test), Q value = 0.21

Table S7. Gene #9: 'del_6q13' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 6(6Q13) MUTATED | 6 | 3 | 7 | 5
DEL PEAK 6(6Q13) WILD-TYPE | 8 | 6 | 0 | 1

Figure S7. Get High-res Image Gene #9: 'del_6q13' versus Molecular Subtype #1: 'CN_CNMF'

'del_9q21.11' versus 'RPPA_CHIERARCHICAL'

P value = 0.0115 (Fisher's exact test), Q value = 0.21

Table S8. Gene #11: 'del_9q21.11' versus Molecular Subtype #4: 'RPPA_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 6 | 7 | 8 | 9
DEL PEAK 8(9Q21.11) MUTATED | 4 | 3 | 7 | 1
DEL PEAK 8(9Q21.11) WILD-TYPE | 2 | 4 | 1 | 8

Figure S8. Get High-res Image Gene #11: 'del_9q21.11' versus Molecular Subtype #4: 'RPPA_CHIERARCHICAL'

'del_12q24.13' versus 'CN_CNMF'

P value = 0.0192 (Fisher's exact test), Q value = 0.21

Table S9. Gene #14: 'del_12q24.13' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 11(12Q24.13) MUTATED | 1 | 4 | 0 | 3
DEL PEAK 11(12Q24.13) WILD-TYPE | 13 | 5 | 7 | 3

Figure S9. Get High-res Image Gene #14: 'del_12q24.13' versus Molecular Subtype #1: 'CN_CNMF'

'del_13q21.32' versus 'CN_CNMF'

P value = 0.0175 (Fisher's exact test), Q value = 0.21

Table S10. Gene #15: 'del_13q21.32' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 12(13Q21.32) MUTATED | 5 | 1 | 5 | 5
DEL PEAK 12(13Q21.32) WILD-TYPE | 9 | 8 | 2 | 1

Figure S10. Get High-res Image Gene #15: 'del_13q21.32' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q22.1' versus 'RPPA_CHIERARCHICAL'

P value = 0.00744 (Fisher's exact test), Q value = 0.21

Table S11. Gene #16: 'del_14q22.1' versus Molecular Subtype #4: 'RPPA_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 6 | 7 | 8 | 9
DEL PEAK 13(14Q22.1) MUTATED | 0 | 2 | 6 | 1
DEL PEAK 13(14Q22.1) WILD-TYPE | 6 | 5 | 2 | 8

Figure S11. Get High-res Image Gene #16: 'del_14q22.1' versus Molecular Subtype #4: 'RPPA_CHIERARCHICAL'

'del_14q32.11' versus 'CN_CNMF'

P value = 0.00034 (Fisher's exact test), Q value = 0.017

Table S12. Gene #17: 'del_14q32.11' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 14(14Q32.11) MUTATED | 2 | 6 | 6 | 6
DEL PEAK 14(14Q32.11) WILD-TYPE | 12 | 3 | 1 | 0

Figure S12. Get High-res Image Gene #17: 'del_14q32.11' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.11' versus 'METHLYATION_CNMF'

P value = 0.00943 (Fisher's exact test), Q value = 0.21

Table S13. Gene #17: 'del_14q32.11' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 14 | 10 | 12
DEL PEAK 14(14Q32.11) MUTATED | 4 | 9 | 7
DEL PEAK 14(14Q32.11) WILD-TYPE | 10 | 1 | 5

Figure S13. Get High-res Image Gene #17: 'del_14q32.11' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_14q32.13' versus 'CN_CNMF'

P value = 0.00025 (Fisher's exact test), Q value = 0.017

Table S14. Gene #18: 'del_14q32.13' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 15(14Q32.13) MUTATED | 2 | 6 | 6 | 6
DEL PEAK 15(14Q32.13) WILD-TYPE | 12 | 3 | 1 | 0

Figure S14. Get High-res Image Gene #18: 'del_14q32.13' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.13' versus 'METHLYATION_CNMF'

P value = 0.0103 (Fisher's exact test), Q value = 0.21

Table S15. Gene #18: 'del_14q32.13' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 14 | 10 | 12
DEL PEAK 15(14Q32.13) MUTATED | 4 | 9 | 7
DEL PEAK 15(14Q32.13) WILD-TYPE | 10 | 1 | 5

Figure S15. Get High-res Image Gene #18: 'del_14q32.13' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_14q32.33' versus 'CN_CNMF'

P value = 0.00021 (Fisher's exact test), Q value = 0.017

Table S16. Gene #19: 'del_14q32.33' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 14 | 9 | 7 | 6
DEL PEAK 16(14Q32.33) MUTATED | 2 | 6 | 6 | 6
DEL PEAK 16(14Q32.33) WILD-TYPE | 12 | 3 | 1 | 0

Figure S16. Get High-res Image Gene #19: 'del_14q32.33' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.33' versus 'METHLYATION_CNMF'

P value = 0.0102 (Fisher's exact test), Q value = 0.21

Table S17. Gene #19: 'del_14q32.33' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 14 | 10 | 12
DEL PEAK 16(14Q32.33) MUTATED | 4 | 9 | 7
DEL PEAK 16(14Q32.33) WILD-TYPE | 10 | 1 | 5

Figure S17. Get High-res Image Gene #19: 'del_14q32.33' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_16q23.1' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.019 (Fisher's exact test), Q value = 0.21

Table S18. Gene #20: 'del_16q23.1' versus Molecular Subtype #8: 'MIRSEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6
--- | --- | --- | --- | --- | --- | ---
ALL | 8 | 10 | 4 | 5 | 5 | 4
DEL PEAK 17(16Q23.1) MUTATED | 1 | 2 | 0 | 0 | 4 | 0
DEL PEAK 17(16Q23.1) WILD-TYPE | 7 | 8 | 4 | 5 | 1 | 4

Figure S18. Get High-res Image Gene #20: 'del_16q23.1' versus Molecular Subtype #8: 'MIRSEQ_CHIERARCHICAL'

Methods & Data
Input

- Copy number data file = all_lesions.txt from GISTIC pipeline

- Processed Copy number data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/CHOL-TP/22519029/transformed.cor.cli.txt

- Molecular subtype file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_mergedClustering/CHOL-TP/22541054/CHOL-TP.transferedmergedcluster.txt

- Number of patients = 36

- Number of significantly focal cnvs = 20

- Number of molecular subtypes = 10

- Exclude genes that fewer than K tumors have alterations, K = 3

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[2] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)
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